Thrombocytopenia Microcephaly Syndrome - a novel phenotype associated with ACTB mutations
Sharissa L. Latham,
Patrick Y.A Reinke,
Manuel H Taft,
Michael J. Lyons,
Michael J Friez,
Jennifer A Lee,
Michael C. Frühwald,
Teresa M Neuhann,
Dietmar J. Manstein,
Natalia Di Donato
Posted 18 Apr 2018
bioRxiv DOI: 10.1101/303909
Posted 18 Apr 2018
The human genome encodes six actin isoforms, produced in a time- and tissue-specific manner during development. Until now mutations in ACTB, encoding beta-cytoplasmic actin (lower case Greek beta-CYA), were exclusively associated with Baraitser-Winter Cerebrofrontofacial syndrome (BWCFF), a complex developmental disorder 1,2. Here, we report 6 patients with de novo heterozygous variants in ACTB, without BWCFF features, who presented with mild microcephaly and thrombocytopenia. Patient primary fibroblasts, utilized to assess the cell-based consequences of these mutations as well as any compensatory effects, show aberrant behavior consistent with a contractile phenotype. A discrete actin filament population, comprising force generating and transmitting actin binding proteins (ABP) that have already been associated with thrombocytopenia, is altered in patient cells. Our results describe a new clinical phenotype associated with ACTB mutations, and identify a cytoskeletal protein interaction network crucial for thrombopoiesis.
- Downloaded 394 times
- Download rankings, all-time:
- Site-wide: 59,276
- In genetics: 2,864
- Year to date:
- Site-wide: 40,436
- Since beginning of last month:
- Site-wide: 75,137
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!